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Diuretic or sodium-restricted diet for obstructive sleep apnea-a randomized trial.
Fiori, CZ, Martinez, D, Montanari, CC, Lopez, P, Camargo, R, Sezerá, L, Gonçalves, SC, Fuchs, FD
Sleep. 2018;(4)
Abstract
STUDY OBJECTIVES Interventions that decrease leg fluid retention reduce obstructive sleep apnea (OSA) severity in nonrandomized experiments. We aimed to investigate in a randomized trial the effect of interventions that reduce fluid volume on OSA severity. METHODS Men diagnosed with severe OSA were randomized to receive daily spironolactone 100 mg + furosemide 20 mg or nutritional counseling to sodium-restricted diet plus placebo pill or placebo pill. All participants underwent home sleep apnea testing at baseline and after 1 week follow-up. The change in apnea-hypopnea index (AHI) was the primary outcome. RESULTS The study included 54 participants and all were assessed at follow-up. The average baseline value of the AHI was similar among groups and from baseline to follow-up the AHI reduced 14.4 per cent (δ value -7.3 events per hour; 95% confidence interval, -13.8 to -0.9) in the diuretic group, 22.3 per cent (-10.7; 95% CI, -15.6 to -5.7) in the diet group, and 0.8 per cent (0.4; 95% CI, -2.5 to 3.2) in the placebo group (p = .001 for time × group interaction). None of the patients had their AHI returned to normal. The reduction in the total body water was 2.2 ± 2.2 L in the diuretic group (p < .001) and 1.0 ± 1.6 l in the low salt diet group (p = .002). Sleepiness and neck circumference were significantly reduced only in the diet group (p = .007 and p < .001 for the time × group interactions, respectively). CONCLUSIONS Interventions to reduce bodily fluid content in men with severe OSA promoted a limited decrease of apnea frequency. This finding suggests that rostral fluid displacement affects only partially the OSA severity and/or that other factors prevail in determining pharyngeal collapsibility. CLINICAL TRIAL Sodium-Restricted Diet and Diuretic in the Treatment of Severe Sleep Apnea (DESALT), https://clinicaltrials.gov/ct2/show/NCT01945801 ClinicalTrials.gov number: NCT01945801.
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[Hyperkalemia treatment in chronic kidney disease patients: overview on new K binders and possible therapeutic approaches].
De Stefano, T, Borrelli, S, Garofalo, C, Provenzano, M, De Nicola, L, Minutolo, R, Conte, G
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. 2018;(5)
Abstract
Hyperkalaemia is a common complication in patients with nondialysis Chronic Kidney Disease (CKD). It is associated with weakness, paralysis, arrhythmias and increased mortality. Higher serum potassium levels refractory to treatment is one of the most frequent reasons to initiate immediately renal replacement treatment in advanced stages of CKD. Hyperkalaemia is also indirectly associated with the progression of CKD; in fact higher serum potassium levels may lead to withdrawal of renin-angiotensin-system inhibiting drugs that currently represent the most effective tools to postpone ESRD. It is therefore essential to identify patients at higher risk of increase of serum K and to implement therapeutic interventions aimed at preventing and treating hyperkalaemia, such as diet modifications and greater use of diuretics and cation exchange resins. Sodium and calcium-polystyrenesulfonate (SPS) are the resins currently available in Italy. However, few studies showed that SPS is efficacious to reduce serum K and is associated with increased risk of severe adverse effects. Patiromer and ZS-9 represent a significant pharmacological progress in the treatment of hyperkalemia. Indeed, recent studies showed that these novel resins are efficient to reduce serum levels of K with minor occurrence of side effects than polystyrensulfonates. Furthermore, Patiromer, sodium free agent, might have a further advantage in CKD patients, reducing the salt intake in these patients. In addition, ZS-9, being fast-acting drug, might be used also in the treatment of acute hyperkalaemia.
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Impact of Intensive Versus Standard Blood Pressure Management by Tertiles of Blood Pressure in SPRINT (Systolic Blood Pressure Intervention Trial).
Shapiro, BP, Ambrosius, WT, Blackshear, JL, Cushman, WC, Whelton, PK, Oparil, S, Beddhu, S, Dwyer, JP, Gren, LH, Kostis, WJ, et al
Hypertension (Dallas, Tex. : 1979). 2018;(6):1064-1074
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Abstract
Intensive systolic blood pressure (SBP) control improved outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Our objective was to expand on reported findings by analysis of baseline characteristics, primary outcomes, adverse events, follow-up blood pressure, and medication use differences by baseline SBP (tertile 1 [T1], <132; tertile 2 [T2], 132-145; and tertile 3 [T3], >145 mm Hg). Participants with higher baseline SBP tertile were more often women and older, had higher cardiovascular risk, and lower utilization of antihypertensive medications, statins, and aspirin. Achieved SBP in both treatment arms was slightly higher in T2 and T3 compared with T1 and fewer in the T3 groups achieved SBP targets compared with T1 and T2 groups. The primary composite outcome with intensive versus standard SBP treatment was reduced by 30% in T1, 23% in T2, and 17% in T3 with no evidence of an interaction (P=0.77). Event rates were lower in the intensive arm, and there was no evidence that this benefit differed by SBP tertile. There was no difference in the hazard for serious adverse events in any of the 3 tertiles. Medication utilization differed across the SBP tertiles at baseline with a lesser percentage of diuretics and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker drugs in the higher tertiles-a finding that reversed during the trial. The beneficial effects of intensive SBP lowering were not modified by the level of baseline SBP. Within the parameters of this population, these findings add support for clinicians to treat blood pressure to goal irrespective of baseline SBP.
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Prevention of postcontrast acute kidney injury after percutaneous transluminal angioplasty by inducing RenalGuard controlled furosemide forced diuresis with matched hydration: study protocol for a randomised controlled trial.
Bolt, LJJ, Sigterman, TA, Krasznai, AG, Sikkink, CJM, Schurink, GH, Bouwman, LH
BMJ open. 2018;(9):e021842
Abstract
INTRODUCTION Percutaneous transluminal angioplasty (PTA) is often complicated due to postcontrast acute kidney injury (PC-AKI) in patients diagnosed with chronic kidney disease (CKD). Hydration therapy is the cornerstone in the prevention of PC-AKI. Furosemide forced diuresis with matched hydration using the RenalGuard system enables a steady balance between diuresis and hydration. A randomised controlled trial will be performed in order to investigate whether furosemide forced diuresis with matched hydration in combination with the RenalGuard system decreases incidence of PC-AKI in patients with CKD receiving a PTA of the lower extremities. Furthermore, we will investigate whether sampling of urine biomarkers 4 hours after intervention can detect PC-AKI in an earlier stage compared with the golden standard, serum creatinine 48-72 hours postintervention. METHODS AND ANALYSIS A single-centre randomised controlled trial will be conducted. Patients >18 years in need of a PTA of the lower extremities and diagnosed with CKD will be randomly assigned to receive either standard of care prehydration and posthydration or furosemide forced diuresis with matched hydration periprocedural using the RenalGuard system. Four hours postintervention, a urine sample will be collected of all participating patients. Serum creatinine will be sampled within 10 days prior to intervention as well as 1, 3 and 30 days postintervention. The primary endpoint is incidence of PC-AKI post-PTA. Secondary endpoint is the rise of urine biomarkers 4 hours postintervention. ETHICS AND DISSEMINATION Study protocol is approved by the research ethics committee and institutional review board (reference number 16 T-201 and NL59809.096.16). Study results will be disseminated by oral presentation at conferences and will be submitted to a peer-reviewed journal. It is anticipated that study results will offer a solution to contrast-induced nephropathy in patients with CKD receiving a PTA of the lower extremities. TRIAL REGISTRATION NUMBER NTR6236; Pre-results. EUDRACT NUMBER 2016-005072-10.
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[Which place for thiazide and thiazide-like diuretics in patients with type 2 diabetes ?].
Scheen, AJ, Krzesinski, JM
Revue medicale de Liege. 2018;(4):176-182
Abstract
The use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. However, these metabolic disturbances are less marked with low-dose of hydrochlorothiazide and with thiazide-like diuretics such as chlorthalidone and indapamide. In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazide(-like) diuretics resulted in a significant reduction in cardiovascular events, all-cause mortality and hospitalization for heart failure compared to placebo. Furthermore, they were shown to be non-inferior to other antihypertensive agents, including blockers of the renin-angiotensin system in diabetic patients without albuminuria. Benefits attributed to thiazide(-like) diuretics (especially at low dose) in terms of cardiovascular protection outweigh the risk of worsening glucose control and inducing other metabolic disorders in patients with type 2 diabetes. Thus low dose thiazide(-like) drugs still play a major role in the treatment of hypertension in patients with type 2 diabetes.
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Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head meta-analysis.
Roush, GC, Abdelfattah, R, Song, S, Kostis, JB, Ernst, ME, Sica, DA
Journal of hypertension. 2018;(6):1247-1255
Abstract
BACKGROUND Found in 36-41% of hypertension, elevated left ventricular mass (LVM) independently predicts cardiovascular events and total mortality. Conversely, drug-induced regression of LVM predicts improved outcomes. Previous studies have favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives for reducing LVM but ignored differences among thiazide-type diuretics. From evidence regarding potency, cardiovascular events, and electrolytes, we hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for reducing LVM. METHOD AND RESULTS Systematic review yielded 12 relevant double-blind randomized trials. CHIPs were more closely associated with reduced LVM than HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic separately. Publication bias favoring RASIs was corrected by cumulative analysis. For reducing LVM, HCTZ tended to be less effective than RASIs. However, the following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to -0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002. Statistical significance (P < 0.05) did not depend on any one trial. CHIPs reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended to increase with trial duration, from a negligible effect at 0.5 year to a maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight percent of patients had information on echocardiographic components of LVM: relative to RASIs, CHIPs significantly reduced end-diastolic LV internal dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence favoring CHIPs over RASIs was at least moderate. CONCLUSION In these novel results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and EDLVID.
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Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis.
Hallow, KM, Helmlinger, G, Greasley, PJ, McMurray, JJV, Boulton, DW
Diabetes, obesity & metabolism. 2018;(3):479-487
Abstract
The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than that of other diuretic classes, results in greater electrolyte-free water clearance and, ultimately, in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling and organ perfusion. We utilize a mathematical model to illustrate that electrolyte-free water clearance results in a greater reduction in IF volume compared to blood volume, and that this difference may be mediated by peripheral sequestration of osmotically inactive sodium. By coupling the model with data on plasma and urinary sodium and water in healthy subjects who received either the SGLT2i dapagliflozin or loop diuretic bumetanide, we predict that dapagliflozin produces a 2-fold greater reduction in IF volume compared to blood volume, while the reduction in IF volume with bumetanide is only 78% of the reduction in blood volume. Heart failure is characterized by excess fluid accumulation, in both the vascular compartment and interstitial space, yet many heart failure patients have arterial underfilling because of low cardiac output, which may be aggravated by conventional diuretic treatment. Thus, we hypothesize that, by reducing IF volume to a greater extent than blood volume, SGLT2 inhibitors might provide better control of congestion without reducing arterial filling and perfusion.
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Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): protocol for a randomized double-blind placebo-controlled trial.
Dhayat, NA, Faller, N, Bonny, O, Mohebbi, N, Ritter, A, Pellegrini, L, Bedino, G, Schönholzer, C, Venzin, RM, Hüsler, C, et al
BMC nephrology. 2018;(1):349
Abstract
BACKGROUND Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. METHODS The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. DISCUSSION The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. TRIAL REGISTRATION ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.
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Type 2 Diabetes and Thiazide Diuretics.
Scheen, AJ
Current diabetes reports. 2018;(2):6
Abstract
PURPOSE OF REVIEW In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. RECENT FINDINGS These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in type 2 diabetes and of new-onset diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with type 2 diabetes and hypertension.
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Randomized Phase II Study Comparing Mannitol with Furosemide for the Prevention of Renal Toxicity Induced by Cisplatin-based Chemotherapy with Short-term Low-volume Hydration in Advanced Non-small Cell Lung Cancer: The OLCSG1406 Study Protocol.
Makimoto, G, Ichihara, E, Hotta, K, Ninomiya, K, Oze, I, Minami, D, Ninomiya, T, Kubo, T, Ohashi, K, Tabata, M, et al
Acta medica Okayama. 2018;(3):319-323
Abstract
Although cisplatin-based chemotherapy shows a survival advantage compared to carboplatin for treating advanced non-small cell lung cancer, high-volume hydration and a long infusion time are necessary to avoid nephrotoxicity, and cisplatin-based chemotherapy has been difficult to administer in outpatient settings. A low-volume hydration method using mannitol or furosemide as forced diuresis was recently introduced, but there are no clear conclusions regarding which agent should be used. We describe our ongoing randomized phase II trial (the OLCSG1406 Study) evaluating the efficacy of forced diuresis. This study will clarify whether mannitol or furosemide is more suitable in cisplatin-based chemotherapy with low-volume hydration.